Characteristics of HPV-specific antibody responses induced by infection and vaccination: cross-reactivity, neutralizing activity, avidity and IgG subclasses

PLoS One. 2013 Sep 18;8(9):e74797. doi: 10.1371/journal.pone.0074797. eCollection 2013.


Objectives: In order to assess HPV-specific IgG characteristics, we evaluated multiple aspects of the humoral antibody response that will provide insight in the HPV humoral immune response induced by HPV infection and vaccination.

Methods: Cross-reactivity of HPV-specific antibodies induced by infection or vaccination was assessed with VLP16 or 18 inhibition using a VLP-based multiplex immunoassay (MIA) for HPV16, 18, 31, 33, 45, 52 and 58. HPV16/18 specific IgG1-4 subclasses and avidity were determined with the VLP-MIA in sera after HPV infection and after vaccination. Neutralizing antibodies were determined in a small subset of single-seropositive and multi-seropositive naturally derived antibodies.

Results: Naturally derived antibodies from single-positive sera were highly genotype-specific as homologue VLP-inhibition percentages varied between 78-94%. In multi-positive sera, cross-reactive antibodies were observed both within and between α7 and α9 species. After vaccination, cross-reactive antibodies were mainly species-specific. Avidity of vaccine-derived HPV-specific antibodies was 3 times higher than that of antibodies induced by HPV infection (p<0.0001). IgG1 and IgG3 were found to be the predominant subclasses observed after HPV infection and vaccination. In the small subset tested, the number of single-positive sera with neutralizing capacity was higher than of multi-positive sera.

Conclusion: Naturally derived HPV-specific antibodies from single-positive samples showed different characteristics in terms of cross-reactivity and neutralizing capacity compared with antibodies from multi-positive sera. Post-vaccination, HPV antibody avidity was approximately 3 times higher than antibody avidity induced by HPV infection. Therefore, antibody avidity might be a potential surrogate of protection.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antibody Affinity / immunology*
  • Antibody Formation / immunology*
  • Child
  • Child, Preschool
  • Cross Reactions / immunology*
  • Female
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / immunology
  • Species Specificity
  • Vaccination*
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Papillomavirus Vaccines

Grant support

The authors have no support or funding to report.